O-04: INCIDENCE OF VASO-OCCLUSIVE CRISES IN PATIENTS WITH SICKLE CELL DISEASE (SCD) AND A HIGH BASELINE DISEASE BURDEN TREATED WITH CRIZANLIZUMAB IN A REAL-WORLD SETTING: RESULTS FROM A MANAGED ACCESS PROGRAM (MAP)
Authors: SILVA-PINTO A., COLOMBATTI R., PASANISI A., ARCIONI F., DEBONNETT L., SOLIMAN W., SARKAR R., CANÇADO R.
Journal: HemaSphere (2022)

Purpose: Vaso-occlusive crises (VOCs) are the hallmark of SCD and can lead to serious complications. P-selectin is a cell adhesion protein that plays a key role in the multicellular interactions that lead to VOCs. Crizanlizumab, a first-in-class humanized monoclonal antibody that blocks P-selectin, is approved in several regions to prevent/reduce VOCs for SCD patients aged ≥16 years. Since June 2018, patients in some countries have received crizanlizumab before health authority approval via a MAP (NCT03720626). Materials and methods: The MAP was designed to provide access to crizanlizumab for patients with a serious or life-threatening disease (SCD) for which no comparable or satisfactory alternative to crizanlizumab was available in their country. Other eligibility criteria included: aged 16–70 years (18–70 years in Italy); history of VOCs as determined by the treating physician (including recurrent VOCs while taking preventative therapies eg hydroxyurea [HU]); and ineligibility for a crizanlizumab clinical trial. Patients’ disease burden during the baseline period was provided by the treating physician. This analysis describes the rate of VOCs and use of opioids for VOC-related pain relief 12 months before crizanlizumab initiation (baseline period) and after ≥12 months of crizanlizumab treatment in patients with SCD participating in the MAP, overall and stratified by genotype and prior HU use (in countries where publication of these data is allowed). Results: As of February 2022, 188 patients have received crizanlizumab in the MAP; 87 have been treated for ≥12 months (Brazil, n=79 [91%]; Italy, n=5 [6%]; Spain, n=2 [2%]; Israel, n=1 [1%]). Median (interquartile range [IQR]) age of the 87 patients was 33 (25–40) years, 57% were female, 45% were African American, 8% Caucasian, 20% Hispanic and 28% of ‘other’ ethnicity; 82% had an HbSS genotype. Prior HU use was reported for 41/56 (73%) patients with available data. During the baseline period, 85% (n=74/87) of patients were hospitalized for a total of 220 SCD-related complications. Crizanlizumab led to a median (IQR) absolute reduction from baseline of –3.0 (–6.0 to –1.0) home-managed and –2.0 (–4.0 to 0) healthcare-managed VOCs after ≥12 months of treatment. Similar reductions in VOC rates post- versus pre-crizanlizumab were observed when stratifying the data by SCD genotype/prior HU use (Figure), although some groups only contain a small number of patients. Opioids were taken for VOC-related pain relief by 95% of patients (n=83/87) at baseline and by 69% (n=60/87) in the 12 months after crizanlizumab treatment. Adverse events were consistent with those reported in other crizanlizumab studies. Conclusion: Patients in the crizanlizumab MAP had significant disease burden at baseline, as evidenced by the high rate of home- and healthcare-managed VOCs, proportion of patients with SCD-related complications and use of opioids for VOC-related pain relief, despite many patients reporting prior HU use. Crizanlizumab led to clinically relevant reductions from baseline in the median annualized rates of home- and healthcare-managed VOCs and use of opioids in this real-world setting, consistent with results from SUSTAIN.L. DEBONNETT declares a conflict of interest: Stock shareholder: Employee and stock shareholder in Novartis Pharmaceuticals